Pfs230 yields higher malaria transmission–blocking vaccine activity than Pfs25 in humans but not mice

Healy, Sara A.; Anderson, Charles; Swihart, Bruce J.; Mwakingwe, Agnes; Gabriel, Erin E.; Decederfelt, Hope; Hobbs, Charlotte V.; Rausch, Kelly M.; Zhu, Daming; Muratova, Olga; Herrera, Raúl; Scaria, Puthupparampil V.; MacDonald, Nicholas J.; Lambert, Lynn; Zaidi, Irfan; Coelho, Camila H.; Renn, Jonathan P.; Wu, Yimin; Narum, David L.; Duffy, Patrick E.

doi:10.1172/jci146221

Cited by 64 publications

(78 citation statements)

References 36 publications

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“…Transmission-blocking activity of antibody against Pfs230 is known to be dependent on antibody mediated complement fixation 25 , 35 . Hence Pfs230 vaccines that generate antibody subclasses that facilitate complement activation may provide higher functional activity.…”

Section: Resultsmentioning

confidence: 99%

“…Earlier studies in mice showed induction of IgG2, that facilitate complement activation in mice, resulted in superior functional activity for Pfs230 conjugate vaccines 32 . Pfs230-EPA conjugate formulated in Alhydrogel ® generated complement fixing IgG1 in humans and Rhesus and showed transmission-blocking functional activity 35 . Therefore, we analyzed the IgG subclass distribution of Pfs230D1-EPA/ALFQ at different time points to evaluate its role in the transmission-blocking activity of this vaccine.…”

Section: Resultsmentioning

confidence: 99%

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Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

et al. 2021

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Malaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

et al. 2021

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“…Although this vaccine approach does not offer any direct clinical protection in humans, blocking malaria transmission is an essential component of effective control and elimination strategies. There has been limited progress for transmission-blocking vaccines, with one candidate based on the gametocyte surface antigen, Pfs230 (Pfs230D1M), showing promise in early clinical trials and a phase 2 clinical trial is ongoing in Mali (NCT03917654) 13 .…”

Section: Developing Vaccines That Block Malaria Transmissionmentioning

confidence: 99%

Recent clinical trials inform the future for malaria vaccines

et al. 2021

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Malaria vaccines are urgently needed in the fight against this devastating disease that is responsible for almost half a million deaths each year. Here, we discuss recent clinical advances in vaccine development and highlight ongoing challenges for the future.Malaria is one of the most devastating infectious diseases in humans, responsible for >200 million cases and almost half a million deaths annually. Control programs have significantly reduced disease burden since 2000, but numbers have plateaued since 2015. The disruption caused by the ongoing COVID-19 pandemic will further unwind these efforts and is predicted to increase the number of malaria deaths. New control measures are urgently needed, and lessons learned from emerging diseases such as COVID-19 highlight the enormous potential of effective vaccines. This has been recognized by the World Health Organization (WHO) and key stakeholders who recommend that, within the next decade, a vaccine should be developed that is at least 75% efficacious against malaria over 2 years (i.e., reduces disease occurrence by at least 75% in vaccinated compared to unvaccinated individuals) and also reduces malaria transmission.Plasmodium falciparum causes the majority of malaria burden and has been the primary focus of vaccine development, and Plasmodium vivax is the second major cause of malaria. There are several vaccine strategies that target different developmental stages of the malaria-causing parasite (Fig. 1). This begins with the sporozoite parasite form, which is inoculated into the skin by a feeding mosquito, circulates in the blood, and infects the liver to develop into the morphologically distinct merozoite form. Merozoites then replicate within red blood cells to exponentially increase parasitemia and can cause severe disease pathology. Some merozoites will undergo development into the gametocyte form that can be taken up by the mosquito vector and subsequently be transmitted in a population. An important bottleneck in the vaccine development pipeline is the assessment of potential candidates in clinical trials. Given the limitations of malaria animal models to adequately reflect human disease, the controlled human malaria infection (CHMI) model offers a unique ability to fast-track initial evaluations of vaccine efficacy. Safe and controlled parasite infection in a clinical setting has proven more time-efficient and less variable than natural parasite exposure and can therefore rely on fewer subjects for conducting the first efficacy trial with a vaccine. CHMI has also been increasingly implemented in malaria-endemic settings, which is critically important to understand the dynamics between vaccine-induced immunity and pre-existing immunity during ongoing natural exposure to malaria.Here, we discuss recent advances and insights from clinical trials of malaria vaccines and highlight ongoing challenges and priorities for the future. Table 1 lists the key trials discussed in this Comment.

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“…In USA adults, two vaccine doses induced functional activity in Pfs230D1M-EPA/Alum volunteers, but no significant activity in Pfs25-EPA vaccine recipients, and combination with Pfs25-EPA did not increase functional activity over Pfs230D1M-EPA alone. The research group concluded that the functional activity of Pfs230D1M-EPA is significantly superior to that of Pfs25-EPA ( Healy et al, 2021 ). For more information about the clinical development of these falciparum TBVs, please refer to two recent review articles ( Miura et al, 2019 ; Duffy, 2021 ).…”

Section: Tbv Development Efforts To Datementioning

confidence: 99%

Identification of Novel Malaria Transmission-Blocking Vaccine Candidates

Takashima

Tachibana

Morita

et al. 2021

Front. Cell. Infect. Microbiol.

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Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.

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Pfs230 yields higher malaria transmission–blocking vaccine activity than Pfs25 in humans but not mice

Cited by 64 publications

References 36 publications

Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

Recent clinical trials inform the future for malaria vaccines

Identification of Novel Malaria Transmission-Blocking Vaccine Candidates

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